The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count
This study was conceived in order to explain what the investigators previously observed suggesting that lisinopril, a drug normally used to treat patients with high blood pressure and heart failure, may be effective in treating infertile men with low sperm count. The investigators hypothesized, therefore, that the drug will not only improve sperm quantity and quality but also increase the fertility in such patients. The investigators first of all reviewed the results of previously published investigations and found out that there was only a few previous studies done in humans.with this class of drugs. Besides, the methods used in conducting most of those studies have been so faulted that the results cannot be trusted to be showing the true picture. The investigators looked at the various faults pointed out with respect to the their design and conduct and took care of them while designing the investigators own study. This was an attempt to provide more credible answers to the question of whether lisinopril, and possibly other drugs of similar mode of action, can be useful in rectifying the problem of infertility caused by low sperm count and , if so, whether it will be safe to use it in people who do not have high blood pressure or heart failure. In order to achieve this the investigators studied 33 patients with sperm of low cell concentration, low percentage of motile cells and high percentage of abnormal cells from no known cause. The patients were randomly allocated to receive either lisinopril 2.5mg daily (17 patients) or daily placebo (16 patients)and their sperm characteristics were examined at intervals, starting from the beginning of the study until when it ended 282 weeks later. The patients were also monitored for adverse events throughout the period. The data form all the patients that took part in the random allocation of treatments at the beginning of the study were included in the analysis that followed, irrespective of whether they completed the study or not.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A 5-year Prospective, Placebo-controlled, Crossover Evaluation of the Efficacy and Tolerability of Low-dose Lisinopril in Normotensives With Idiopathic Oligospermic Infertility|
- Changes From Baseline in the Seminal Fluid Characteristics Throughout the Study [ Time Frame: Week 96. ] [ Designated as safety issue: No ]The seminal fluid characteristics were assessed twice before the entry of each patient and both at least two-weeks apart. The two values were averaged and recorded as baseline for week 0 while subsequent changes from the baseline were monitored during each of the scheduled visits at weeks 6, 12, 24, 48, 96, 102, 114, 138, 186 and 282. The two groups swopped treatments at the 96th week. The number of pregnancies achieved was also documented throughout the study period.
- Total Sperm Cell Count Per Milliliter of Seminal Fluid. [ Time Frame: Week 96 ] [ Designated as safety issue: No ]the number of sperm cells counted per milliliter volume of seminal fluid
- Proportion of Sperm Cells With Normal Motility (%) [ Time Frame: Week 96 ] [ Designated as safety issue: No ]This was determined as the proportion (percent) of the total sperm cells exhibiting both rhythmic and propulsive movements considered to be of normal intensity.
- Proportion of Sperm Cells With Abnormal Morphology (%) [ Time Frame: Week 96 ] [ Designated as safety issue: No ]Proportion (per cent) of sperm cells with abnormal appearance
- Ejaculate Volume [ Time Frame: Week 282 ] [ Designated as safety issue: No ]The volume in milliliters of seminal fluid produced per ejaculation.
- Total Sperm Cell Count [ Time Frame: Week 282 ] [ Designated as safety issue: No ]The total number of sperm cells found in each milliliter of seminal fluid.
- Proportion of Sperm Cells With Normal Motility (%) [ Time Frame: Week 282 ] [ Designated as safety issue: No ]The proportion (per cent) of the sperm cells exhibiting both rhythmic and propulsive movements considered to be of normal intensity.
- Proportion of Sperm Cells With Abnormal Morphology (%) [ Time Frame: Week 282 ] [ Designated as safety issue: No ]The proportion (per cent) of the total number of sperm cell with abnormal appearance.
- Adverse Events Monitoring [ Time Frame: At weeks 6, 12, 24, 48, 96, 102, 114,138, 186 and 282 ] [ Designated as safety issue: Yes ]The patients were encouraged to report every event promptly by phone to one of the authors (NOG), no matter however minor.Blood pressure measurements were done with mercury sphygmomanometers fitted with adult-size cuffs (Accoson, England). Serum potassium levels were estimated using the flame photometric method as described by Davidson and Henry
|Study Start Date:||March 1998|
|Study Completion Date:||December 2006|
|Primary Completion Date:||December 2006 (Final data collection date for primary outcome measure)|
Placebo Comparator: Sugar pill
Started with Placebo until the crossover.
Started with Lisinopril until the crossover
The two groups of patients, A and B, were randomly allocated treatments in a double-blind fashion. Group A was started on the coded drug "DY1" while group B was started on the coded drug "DZ2". Both "DY1" and "DZ2" were very identical in appearance. At week 96 the drugs were swopped between the groups such that group A changed to drug "DZ2" while group B changed to drug "DY1". There was no intervening washout period. The codes were concealed until after the data analysis.
Other Name: (Zestril®, AstraZeneca Pharmaceuticals,Washington NC, USA)
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01409837
|University of Nigeria Teaching Hospital, Ituku-Ozalla,|
|Enugu, Nigeria, 01129|
|Principal Investigator:||Anthony U Mbah, MD, FMCP||University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu|